Disorders of Sleep and Wakefulness and their Treatment

• Neurobiology of sleep and wakefulness
• The arousal spectrum
• Sleep/wake switch
• Histamine
• Insomnia and hypnotics
• What is insomnia?
• Chronic treatment for chronic insomnia?
• Benzodiazepine hypnotics
• GABA-A positive allosteric modulators (PAMs) as hypnotics
• Psychiatric insomnia and the GABA-A PAMs
• Melatonergic hypnotics
• Serotonergic hypnotics
• Histamine H1 antagonists as hypnotics
• Who cares about slow-wave sleep?
• The hypnotic pharmacy
• Excessive daytime sleepiness (hypersomnia) and wake-promoting agents
• What is sleepiness?
• How sleepy is sleepiness?
• What’s wrong with being sleepy?
• Mechanism of action of wake-promoting agents
• The wake-up pharmacy
• Summary

Disorders of Sleep and Wakefulness and their Treatment

This chapter provides a brief overview of the psychopharmacology of disorders of sleep and wakefulness. Included here are short discussions of the symptoms, diagnostic criteria, and treatments for disorders that cause insomnia, excessive daytime sleepiness, or both. Clinical descriptions and formal criteria for how to diagnose sleep disorders are mentioned here only in passing. The reader should consult standard reference sources for this material. The discussion here emphasizes the links between various brain circuits and their neurotransmitters with disorders that cause insomnia or sleepiness. The goal of this chapter is to acquaint the reader with ideas about the clinical and biological aspects of sleep and wakefulness, how various disorders can alter sleep and wakefulness, and how many new and evolving treatments can resolve the symptoms of insomnia and sleepiness.

The detection, assessment, and treatment of sleep/wake disorders are rapidly becoming standardized parts of a psychiatric evaluation. Modern psychopharmacologists increasingly consider sleep to be a psychiatric “vital sign,” thus requiring routine evaluation and symptomatic treatment whenever a sleep problem is encountered. This is similar to the earlier discussion in Chapter 15, where pain is also increasingly being considered as another psychiatric vital sign. That is, disorders of sleep (and pain) are so important, so pervasive, and cut across so many psychiatric conditions that the elimination of these symptoms – no matter what psychiatric disorder may be present – is increasingly recognized as necessary in order to achieve full symptomatic remission for the patient.

Many of the treatments discussed in this chapter are covered in previous chapters. For details of mechanisms of insomnia treatments that are also used for the treatment of depression, the reader is referred to Chapter 12; for those insomnia treatments that share the same mechanism of action with various benzodiazepine anxiolytics, the reader is referred to Chapter 14. For various hypersomnia treatments, especially stimulants, the reader is referred to Chapter 4, which introduces drugs that target monoamine transporters, and also to Chapter 17, on ADHD, and Chapter 19, on drug abuse as well as the use and abuse of stimulants. The discussion in this chapter is at the conceptual level, not at the pragmatic level. The reader should consult standard drug handbooks (such as Essential Psychopharmacology: Prescriber’s Guide) for details of doses, side effects, drug interactions, and other issues relevant to the prescribing of these drugs in clinical practice.